Single-cell RNA-seq analysis of rat molars reveals cell identity and driver genes associated with dental mesenchymal cell differentiation

IF 4.4 1区 生物学 Q1 BIOLOGY BMC Biology Pub Date : 2024-09-11 DOI:10.1186/s12915-024-01996-w
Yingchun Zheng, Ting Lu, Leitao Zhang, Zhongzhi Gan, Aoxi Li, Chuandong He, Fei He, Sha He, Jian Zhang, Fu Xiong
{"title":"Single-cell RNA-seq analysis of rat molars reveals cell identity and driver genes associated with dental mesenchymal cell differentiation","authors":"Yingchun Zheng, Ting Lu, Leitao Zhang, Zhongzhi Gan, Aoxi Li, Chuandong He, Fei He, Sha He, Jian Zhang, Fu Xiong","doi":"10.1186/s12915-024-01996-w","DOIUrl":null,"url":null,"abstract":"The molecular mechanisms and signaling pathways involved in tooth morphogenesis have been the research focus in the fields of tooth and bone development. However, the cell population in molars at the late bell stage and the mechanisms of hard tissue formation and mineralization remain limited knowledge. Here, we used the rat mandibular first and second molars as models to perform single-cell RNA sequencing (scRNA-seq) analysis to investigate cell identity and driver genes related to dental mesenchymal cell differentiation during the late bell hard tissue formation stage. We identified seven main cell types and investigated the heterogeneity of mesenchymal cells. Subsequently, we identified novel cell marker genes, including Pclo in dental follicle cells, Wnt10a in pre-odontoblasts, Fst and Igfbp2 in periodontal ligament cells, and validated the expression of Igfbp3 in the apical pulp. The dynamic model revealed three differentiation trajectories within mesenchymal cells, originating from two types of dental follicle cells and apical pulp cells. Apical pulp cell differentiation is associated with the genes Ptn and Satb2, while dental follicle cell differentiation is associated with the genes Tnc, Vim, Slc26a7, and Fgfr1. Cluster-specific regulons were analyzed by pySCENIC. In addition, the odontogenic function of driver gene TNC was verified in the odontoblastic differentiation of human dental pulp stem cells. The expression of osteoclast differentiation factors was found to be increased in macrophages of the mandibular first molar. Our results revealed the cell heterogeneity of molars in the late bell stage and identified driver genes associated with dental mesenchymal cell differentiation. These findings provide potential targets for diagnosing dental hard tissue diseases and tooth regeneration.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12915-024-01996-w","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

The molecular mechanisms and signaling pathways involved in tooth morphogenesis have been the research focus in the fields of tooth and bone development. However, the cell population in molars at the late bell stage and the mechanisms of hard tissue formation and mineralization remain limited knowledge. Here, we used the rat mandibular first and second molars as models to perform single-cell RNA sequencing (scRNA-seq) analysis to investigate cell identity and driver genes related to dental mesenchymal cell differentiation during the late bell hard tissue formation stage. We identified seven main cell types and investigated the heterogeneity of mesenchymal cells. Subsequently, we identified novel cell marker genes, including Pclo in dental follicle cells, Wnt10a in pre-odontoblasts, Fst and Igfbp2 in periodontal ligament cells, and validated the expression of Igfbp3 in the apical pulp. The dynamic model revealed three differentiation trajectories within mesenchymal cells, originating from two types of dental follicle cells and apical pulp cells. Apical pulp cell differentiation is associated with the genes Ptn and Satb2, while dental follicle cell differentiation is associated with the genes Tnc, Vim, Slc26a7, and Fgfr1. Cluster-specific regulons were analyzed by pySCENIC. In addition, the odontogenic function of driver gene TNC was verified in the odontoblastic differentiation of human dental pulp stem cells. The expression of osteoclast differentiation factors was found to be increased in macrophages of the mandibular first molar. Our results revealed the cell heterogeneity of molars in the late bell stage and identified driver genes associated with dental mesenchymal cell differentiation. These findings provide potential targets for diagnosing dental hard tissue diseases and tooth regeneration.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
大鼠臼齿的单细胞 RNA-Seq 分析揭示了与牙齿间充质细胞分化相关的细胞特征和驱动基因
牙齿形态发生的分子机制和信号通路一直是牙齿和骨骼发育领域的研究重点。然而,人们对磨牙晚钟阶段的细胞群以及硬组织形成和矿化机制的了解仍然有限。在这里,我们以大鼠下颌第一和第二磨牙为模型,进行了单细胞 RNA 测序(scRNA-seq)分析,以研究晚钟期硬质组织形成阶段的细胞特征和与牙齿间充质细胞分化相关的驱动基因。我们确定了七种主要细胞类型,并研究了间充质细胞的异质性。随后,我们确定了新的细胞标记基因,包括牙泡细胞中的 Pclo、前牙本质细胞中的 Wnt10a、牙周韧带细胞中的 Fst 和 Igfbp2,并验证了 Igfbp3 在根尖牙髓中的表达。动态模型揭示了间充质细胞的三种分化轨迹,分别源自两种类型的牙泡细胞和根尖牙髓细胞。牙髓尖细胞的分化与 Ptn 和 Satb2 基因有关,而牙泡细胞的分化与 Tnc、Vim、Slc26a7 和 Fgfr1 基因有关。pySCENIC分析了簇特异性调控子。此外,在人牙髓干细胞的牙胚分化过程中验证了驱动基因 TNC 的牙胚功能。在下颌第一磨牙的巨噬细胞中发现破骨细胞分化因子的表达增加。我们的研究结果揭示了臼齿在晚钟阶段的细胞异质性,并确定了与牙齿间充质细胞分化相关的驱动基因。这些发现为诊断牙齿硬组织疾病和牙齿再生提供了潜在的目标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
BMC Biology
BMC Biology 生物-生物学
CiteScore
7.80
自引率
1.90%
发文量
260
审稿时长
3 months
期刊介绍: BMC Biology is a broad scope journal covering all areas of biology. Our content includes research articles, new methods and tools. BMC Biology also publishes reviews, Q&A, and commentaries.
期刊最新文献
Novel function of single-target regulator NorR involved in swarming motility and biofilm formation revealed in Vibrio alginolyticus. Hibernation reduces GABA signaling in the brainstem to enhance motor activity of breathing at cool temperatures. A powerful and versatile new fixation protocol for immunostaining and in situ hybridization that preserves delicate tissues. Bridging chemical structure and conceptual knowledge enables accurate prediction of compound-protein interaction. Evolutionary divergent clusters of transcribed extinct truncated retroposons drive low mRNA expression and developmental regulation in the protozoan Leishmania.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1